Submissions for variant NM_001232.4(CASQ2):c.731A>G (p.His244Arg)

gnomAD frequency: 0.02511  dbSNP: rs28730716

Total submissions: 19

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000037146	SCV000050814	benign	not specified	2013-06-24	criteria provided, single submitter	research
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000037146	SCV000060803	benign	not specified	2012-04-25	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000037146	SCV000111495	benign	not specified	2013-06-10	criteria provided, single submitter	clinical testing
GeneDx	RCV000037146	SCV000167531	benign	not specified	2012-03-19	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Ambry Genetics	RCV000243545	SCV000319118	benign	Cardiovascular phenotype	2015-03-23	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Illumina Laboratory Services, Illumina	RCV000625053	SCV000347681	likely benign	Catecholaminergic polymorphic ventricular tachycardia 2	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000430947	SCV000511177	benign	not provided	2016-07-22	criteria provided, single submitter	clinical testing
Invitae	RCV002513239	SCV000559571	benign	Catecholaminergic polymorphic ventricular tachycardia 1	2024-02-01	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000625053	SCV000743628	benign	Catecholaminergic polymorphic ventricular tachycardia 2	2014-10-09	criteria provided, single submitter	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000625053	SCV000744944	benign	Catecholaminergic polymorphic ventricular tachycardia 2	2015-09-21	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000768702	SCV000900072	benign	Cardiomyopathy	2015-09-17	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000625053	SCV001159262	benign	Catecholaminergic polymorphic ventricular tachycardia 2	2023-10-16	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002490410	SCV002797802	benign	Catecholaminergic polymorphic ventricular tachycardia 1; Catecholaminergic polymorphic ventricular tachycardia 2	2021-08-13	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000625053	SCV004048915	likely benign	Catecholaminergic polymorphic ventricular tachycardia 2	2023-04-11	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001841524	SCV000052074	benign	Cardiac arrhythmia	2015-04-29	no assertion criteria provided	clinical testing
Stanford Center for Inherited Cardiovascular Disease, Stanford University	RCV000037146	SCV000280062	uncertain significance	not specified	2015-10-05	no assertion criteria provided	clinical testing	Note this variant was found in clinical genetic testing performed by one or more labs who may also submit to ClinVar. Thus any internal case data may overlap with the internal case data of other labs. The interpretation reviewed below is that of the Stanford Center for Inherited Cardiovascular Disease. Given this variants presence in a general population sample we consider this a variant of uncertain significance. A polar, positive Histidine is replaced with a polar positive Arginine at position 244 of CASQ2 gene, no net charge change. Other variants in this gene have been associated with CPVT and ARVC. It is listed in dbSNP with a minor allele frequency of 0.02 in the HapMap/1000 genomes YRI sample of 25 individuals from Nigeria. This minor allele frequency would suggest that approximately 1 in 2500 individuals in this population would be homozygotes. The prevalence of CPVT has been estimated at 1/10,000.
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000430947	SCV001799588	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000037146	SCV001923222	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000037146	SCV001959562	benign	not specified		no assertion criteria provided	clinical testing